The spatial orientation of the alpha and beta subunits of the insulin receptor in the rat adipose cell plasma membrane has been examined using lactoperoxidase/NaI125 iodination. The results suggest that the alpha receptor subunit is primarily exposed on the extracellular surface of the plasma membrane while the beta receptor subunit traverses the membrane, and this vectorial disposition is inverted during internalization. The biosynthesis of the insulin receptor has also been studied in primary cultures of isolated rat adipose cells. The results suggest that insulin receptors are synthesized through the formation and processing of a 190K precursor in the endoplasmic reticulum and Golgi followed by insertion of the mature 135K and 95K subunits into the plasma membrane.